Impact of the ingestion of polyphenols and fruits rich in polyphenols on atherosclerosis studied on apoE deficient mice by a transcriptomic approach

摘要

Atherosclerosis is a complex and progressive cardiovascular disease characterised by the accumulation of lipids and fibrous elements in the large arterial (Lusis, 2000). Knowledge on atherosclerosis development and its prevention by polyphenols derives mainly from studies in animal models. Mice deficient in apolipoprotein E (ApoE), a glycoprotein present in all lipoproteins, was created in 1992. Sequential events related to lesion formation observed in these mice are strikingly similar to those in humans (Jawien et al., 2004). This model is the most largely used in genetic and physiological studies of atherosclerosis (Lusis, 2000). This model has also been used to study the impact of polyphenol consumption on atherosclerosis development. Feeding ApoE deficient mice with caffeic acid phenethyl ester, a natural flavonoid, for 12 wk, significantly reduced aortic atherosclerosis development (Hishikawa et al., 2005). Reduction in atherosclerosis lesion size has also been described after feeding mice with grape powder polyphenols; green tea polyphenols; red wine and its major polyphenols (Hayek et al., 1997). Most authors have explained these protective effects of polyphenols by their antioxidant properties and their capacity to inhibit lipid peroxidation. However, it appears today that the mechanisms of action could be much more varied and could depend on gene expression variations. The goal of our study was to identify the impact of the ingestion of major fruit and wine polyphenols on the development of atherosclerosis in apoE deficient mice. Lesion size is assessed by histological analyses of thin sections of the aortic root. In order to understand the key metabolic pathways involved in the prevention of atherosclerosis by polyphenols, global gene expression variations in the aorta are measured using mouse pangenomic microarrays.